Aging is associated with a significant loss of renal function, and is also linked to an increased susceptibility of the kidney to both ischemia and toxic insult. As the maintenance of membrane polarity and transport properties is critical for normal renal function, it is not surprising that several human nephropathies are associated with the loss of cell-cell adhesion, and a functional complex is required for normal organ homeostasis. Given that at least four cadherins (E, K, Ksp, and N) are expressed in the kidney, including the proximal tubule, a comprehensive effort must be made to examine the impact of aging on each of the possible cadherin/catenin complexes. We hypothesize that N-CADHERIN EXPRESSION IS SELECTIVELY LOST IN RENAL PROXIMAL TUBULE EPITHELIUM AND CONTRIBUTES TO AGE-DEPENDENT RENAL DYSFUNCTION. Preliminary data from this laboratory indicates that a selective loss of N-cadherin in the proximal tubular epithelium is associated with aging, in the absence of changes in E- or Ksp-cadherin expression. In addition, no changes were seen in the expression of tight junction or desmosomal components, complexes also involved in cell-cell adhesion. We proposed to examine the age-dependent loss of N-cadherin, and to determine if this loss is organ-specific. Additionally, the expression of N-cadherin in aged kidney will be examined in rat strains that are susceptible and non-susceptible to age-dependent renal dysfunction is requisite for the development of therapeutic strategies for prevention and/or treatment. The proposed studies will begin to establish a role of disruption of the cadherin/catenin complex as an important feature of aging in the kidney.